A Large-Scale, Exome-Wide Association Study of Han Chinese Women Identifies Three Novel Loci Predisposing to Breast Cancer.

Genome-wide association studies have identified more than 90 susceptibility loci for breast cancer. However, the missing heritability is evident, and the contributions of coding variants to breast cancer susceptibility have not yet been systematically evaluated. Here, we present a large-scale whole-exome association study for breast cancer consisting of 24,162 individuals (10,055 cases and 14,107 controls). In addition to replicating known susceptibility loci (e.g., ESR1, FGFR2, and TOX3), we identify two novel missense variants in C21orf58 (rs13047478, Pmeta = 4.52 × 10-8) and ZNF526 (rs3810151, Pmeta = 7.60 × 10-9) and one new noncoding variant at 7q21.11 (P < 5 × 10-8). C21orf58 and ZNF526 possessed functional roles in the control of breast cancer cell growth, and the two coding variants were found to be the eQTL for several nearby genes. rs13047478 was significantly (P < 5.00 × 10-8) associated with the expression of genes MCM3AP and YBEY in breast mammary tissues. rs3810151 was found to be significantly associated with the expression of genes PAFAH1B3 (P = 8.39 × 10-8) and CNFN (P = 3.77 × 10-4) in human blood samples. C21orf58 and ZNF526, together with these eQTL genes, were differentially expressed in breast tumors versus normal breast. Our study reveals additional loci and novel genes for genetic predisposition to breast cancer and highlights a polygenic basis of disease development.Significance: Large-scale genetic screening identifies novel missense variants and a noncoding variant as predisposing factors for breast cancer. Cancer Res; 78(11); 3087-97. ©2018 AACR.

From natural to biomimetic: The superhydrophobicity and the contact time.

The superhydrophobicities and the contact time of lotus leaf and reed leaf were investigated. The results indicated that both lotus leaf and reed leaf have good superhydrophobic properties, and the water contact time was 12.7 and 14.7 ms on the surface of lotus leaf and reed leaf, respectively. Surface structure plays a key role in the different contacting times. Homogeneous distribution of papillae on the surface of lotus leaf was more helpful to reduce the contact time than anisotropic groove-shape on the surface of reed leaf. Based on the bionics coupling theory, the bionics sample possessing similar lotus-leaf-like surface structure on the aluminum alloy was designed and fabricated successfully. The water contact angle was about 153 ± 2°, sliding angle less than 5°, and the water contact time was 13.4 ms on the surface of bionics sample, which presented excellent superhydrophobic property, and achieved the aim of bionic design. Microsc. Res. Tech. 79:712-720, 2016. © 2016 Wiley Periodicals, Inc.

Tenascin-C promotes migration of hepatic stellate cells and production of type I collagen.

Tenascin-C (TN-C) is an extracellular matrix glycoprotein markedly upregulated during liver fibrosis. The study is performed to explore the role of TN-C during the growth and activation of hepatic stellate cells (HSCs). We found that TN-C was accumulated accompanying with the HSC activation. Our data on cell migration assay revealed that the rTN-C treatment enhanced HSC migration in a dose- and time-dependent manner, but did not influence their proliferation. HSCs transfected with pTARGET-TN-C overexpression vector displayed increased the type I collagen (Col I) production. TN-C overexpression enhanced the process of HSC activation through TGF-ß1 signaling. Moreover, the anti-α9ß1 integrin antibody treatment blocked the TN-C-driven Col I increase in rat HSCs. Collectively, TN-C had a positive role in activation of HSCs mediated by TGF-ß1 and α9ß1 integrin, manifesting elevation of Col I production and promotion of cell migration. Our results provide a potential insight for the therapy of hepatic fibrosis.

Amniotic stem cell transplantation therapy for type 1 diabetes: a case report.

This case report presents an evaluation of the clinical effects of an allogeneic amniotic cell transplant for the treatment of type 1 diabetes mellitus. A 26-year-old man with type 1 diabetes was treated with stem cells isolated from his neonatal son's amniotic membrane, collected at birth (2 × 10(7) cells). The cells, which expressed high levels of cluster of differentiation (CD) 133 and CD34 as assessed by flow cytometry, were infused into the pancreatic dorsal artery through the left femoral artery. The main study outcome was the change in exogenous insulin requirements, which began to decrease 3 days after transplantation. At 3 months post-transplantation, the patient was insulin independent and remained so for 6.2 months. During a 36-month follow-up, the patient's blood glucose remained under control and insulin treatment was readjusted to a dosage of 8 IU/day. These preliminary data suggest that amniotic membrane stem cell transplantation can improve islet-cell function in response to glucose in vivo, although an alternative explanation (such as a honeymoon period due to reduced glucose toxicity) also has to be considered.